Ophthalmoplegia: when the tests are all negative, where next?

When persistent neurological symptoms and signs defy diagnostic explanation despite repeated rounds of investigation, how should the clinician proceed? We present a case of this type with an eventual and unusual diagnosis. As well as being an exercise in awareness raising, the case serves as a prelude to considering what practical management strategies might be adopted in the face of persistent diagnostic uncertainty with its consequent frustrations for patient, significant others and physicians. We consider these approaches first with respect to the specific finding of ophthalmoplegia, the principal feature in this case, and second with respect to any neurological diagnosis.